Recently, a new series of potent antileukemic trichothecenes called baccharins and baccharols was isolated from an unexpected source, Baccharis megapotamica, which is a shrub found in Brazil. Previously, all known examples of trichothecenes were derived from microbial sources. The baccharins and baccharols are related to the macrocyclic trichothecenes known as roridins and verrucarins but unlike the latter compounds, baccharins and baccharols have shown very high in vivo activity against P-388 leukemia. The objectives of this proposal are (1) to isolate new and potent anticancer compounds from fungi and higher plant sources; (2) to synthesize derivatives and analogues of active compounds isolated from natural sources. Baccharin-like compounds will be synthesized in the laboratory from the known roridins and verrucarins by chemically altering mycotoxins (i.e. roridins and verrucarins) isolated by standard laboratory fermentation procedures. A 3000 lb extract of B. megapotamica will yield large quantities of baccharins and baccharols, some of which, no doubt, have gone undetected in smaller extracts. New baccharins and baccharols are to be characterized and tested against in vivo tumor systems. Those baccharins and baccarols isolated in large amounts from the extract are to be chemically altered with the aim of increasing in vivo antitumor activity of these compounds.